Process for the preparation of...

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C546S026000, C546S061000, C546S062000, C546S073000, C546S095000, C546S152000, C514S279000, C514S284000, C514S285000

Reexamination Certificate

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06518430

ABSTRACT:

TECHNICAL FIELD
The present invention relates to an efficient process for the preparation of the selective glucocorticoid receptor agents which are useful 5-(substituted)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinolines.
BACKGROUND OF THE INVENTION
The glucocorticoid receptor (GR) has an essential role in regulating human physiology and immune response. Steroids which interact with GR have been shown to be potent anti-inflammatory agents. Steroidal GR ligands, however, have side effects associated with chronic dosing believed to be the result of cross-reactivity with other steroid receptors such as estrogen, progesterone, androgen, and mineralocorticoid receptors which have somewhat homologous ligand binding domains. Therefore, nonsteroidal agents selective for GR are actively being researched for the treatment of inflammation, inflammatory disease, immune and autoimmune diseases.
SUMMARY OF THE INVENTION
The present invention is directed to an efficient process for the preparation of 5-(substituted)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinolines. In particular the present invention is directed to, 5-(allyloxy)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinoline in an overall yield of 24% and with elimination of all column chromatography purification steps.


REFERENCES:
patent: 99/41256 (1999-08-01), None
Coghlan et al. (DN 136:102372, HCAPLUS, abstract of WO 2002002565).*
Coghlan et al. (J. Med. Chem. (2001), 44, (18), 2879-2885).*
Elmore et al. (J. Med. Chem. (2001), 44 (25), 4481-4491).*
James P. Edwards et al, “5-Aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines as Potent, Orally Active, Nonsterodial Progesterone Receptor Agonists: The Effect of D-Ring Substituents”,J. Med. Chem., 1998, vol. 41, p.303-310.

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